9-Deoxy-9-methylene-13,14-didehydro-16-phenyl-PGF compounds

ABSTRACT

The present invention relates to novel 9-deoxy-9-methylene-13,14-didehydro-16-phenyl-PGF compounds. These compounds are useful pharmacological agents, and are useful for the same purposes as the corresponding PGE-type compounds.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation-in-part of Ser. No. 786,249, filed Apr. 11, 1977, now issued as U.S. Pat. No. 4,118,584.

The present invention relates to a novel 9-deoxy-9-methylene-13,14-didehydro-16-phenyl-PGF-compounds, the essential material constituting a disclosure of which is incorporated here by reference from U.S. Pat. No. 4,118,584. 

I claim:
 1. A prostaglandin analog of the formula ##STR1## WHEREIN M₁ is ##STR2## wherein R₅ is hydrogen or methyl; wherein L₁ is ##STR3## wherein R₃ and R₄ are hydrogen, methyl, or fluoro, being the same or different, with the proviso that one of R₃ and R₄ is fluoro only when the other is hydrogen or fluoro;Wherein Z₇ is (1) cis-CH═CH--CH₂ --(CH₂)_(g) --CH₂ --, (2) cis-CH═CH--CH₂ --(CH₂)_(g) --CF₂ --, (3) cis-CH₂ --CH═CH--(C₂)_(g) --CH₂ --, (4) --(ch₂)₃ --(ch₂)_(g) --CH₂ --, or (5) --(CH₂)₃ --(CH₂)_(g) -CF₂ --,wherein G is one, 2, or 3;Wherein T is chloro, fluoro, trifluoromethyl, alkyl of one to 3 carbon atoms, inclusive, or alkoxy of one to 3 carbon atoms, inclusive, and s is zero, one, 2, or 3, the various T(s being the same or different, with the proviso that not more than two T's are other than alkyl; Wherein R₁ is hydrogen, alkyl of one to 12 carbon atoms, inclusive, cycloalkyl of 3 to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbon atoms, inclusive, phenyl, phenyl substituted with one, two, or three chloro or alkyl or one to 3 carbon atoms, inclusive, or a pharmacologically acceptable cation, and the 1,11- or 1,15-lactones thereof.
 2. A prostaglandin analog according to claim 1, wherein Z₇ is cis-CH₂ --CH═CH--(CH₂)_(g) --CH₂ --.
 3. 9-Deoxy-9-methylene-cis-4,5-didehydro-16-phenyl-17,18,19,20-tetranor-13,14-didehydro-PGF₁, a prostaglandin analog according to claim
 2. 4. A prostaglandin analog according to claim 1, wherein Z₇ is --(CH₂)₃ --(CH₂)_(g) --CH₂ --.
 5. A prostaglandin analog according to claim 4, wherein M₁ is ##STR4##
 6. 9-Deoxy-9-methylene-15-epi-16-phenyl-17,18,19,20-tetranor-13,14-didehydro-PGF₁, a prostaglandin analog according to claim
 5. 7. A prostaglandin analog according to claim 4, wherein M₁ is ##STR5##
 8. A prostaglandin analog according to claim 7, wherein s is zero or one and T is chloro, fluoro, or trifluoromethyl.
 9. A prostaglandin analog according to claim 8, wherein g is
 3. 10. 9-Deoxy-9-methylene-2a,2b-dihomo-15-methyl-16-phenyl-17,18,19,20-tetranor-13,14-didehydro-PGF₁, a prostaglandin analog according to claim
 9. 11. 9-Deoxy-9-methylene-2a,2b-dihomo-16-phenyl-17,18,19,20-tetranor-13,14-didehydro-PGF₁, a prostaglandin analog according to claim
 9. 12. A prostaglandin analog according to claim 8, wherein g is one.
 13. A prostaglandin analog according to claim 12, wherein at least one of R₃ and R₄ is methyl.
 14. A prostaglandin analog according to claim 13, wherein R₃ and R₄ are both methyl.
 15. 9-Deoxy-9-methylene-16-methyl-16-phenyl-18,19,20-trinor-13,14-didehydro-PGF₁, a prostaglandin analog according to claim
 14. 16. A prostaglandin analog according to claim 12, wherein at least one of R₃ and R₄ is fluoro.
 17. A prostaglandin analog according to claim 16, wherein R₃ and R₄ are both fluoro.
 18. 9-Deoxy-9-methylene-16,16-difluoro-16-phenyl-17,18,19,20-tetranor-13,14-didehydro-PGF₁, a prostaglandin analog according to claim
 17. 19. A prostaglandin analog according to claim 12, wherein R₃ and R₄ are both hydrogen.
 20. A prostaglandin analog according to claim 19, wherein R₅ is methyl.
 21. 9-Deoxy-9-methylene-15-methyl-16-phenyl-17,18,19,20-tetranor-13,14-didehydro-PGF₁, a prostaglandin analog according to claim
 20. 22. A prostaglandin analog according to claim 19, wherein R₅ is hydrogen.
 23. 9-Deoxy-9-methylene-16-phenyl-17,18,19,20-tetranor-13,14-didehydro-PGF₁, a prostaglandin analog according to claim
 22. 24. A prostacyclin analog according to claim 1, wherein Z₇ is cis-CH═CH--CH₂ --(CH₂)_(g) --CH₂ --.
 25. A prostaglandin analog according to claim 24, wherein M₁ is ##STR6##
 26. A prostaglandin analog according to claim 25, wherein s is zero or one and T is chloro, fluoro, or trifluoromethyl.
 27. A prostaglandin analog according to claim 26, wherein g is
 3. 28. 9-Deoxy-9-methylene-2a,2b-dihomo-15-epi-15-methyl-16-phenyl-17,18,19,20-tetranor-13,14-didehydro-PGF₂, a prostaglandin analog according to claim
 27. 29. 9-Deoxy-9-methylene-2a,2b-dihomo-15-epi-16-phenyl-17,18,19,20-tetranor-13,14-didehydro-PGF.sub.2, a prostaglandin analog according to claim
 27. 30. A prostaglandin analog according to claim 26, wherein g is one.
 31. A prostaglandin analog according to claim 30, wherein at least one of R₃ and R₄ is methyl.
 32. 9-Deoxy-9-methylene-15-epi-16-methyl-16-phenyl-18,19,20-trinor-13,14-didehydro-PGF₂, a prostacyclin analog according to claim
 31. 33. A prostaglandin analog according to claim 30, wherein at least one of R₃ and R₄ is fluoro.
 34. 9-Deoxy-9-methylene-15-epi-16,16-difluoro-16-phenyl-17,18,19,20-tetranor-13,14-didehydro-PGF₂, a prostaglandin analog according to claim
 33. 35. A prostaglandin analog according to claim 30, wherein R₃ and R₄ are both hydrogen.
 36. 9-Deoxy-9-methylene-15-epi-15-methyl-16-phenyl-17,18,19,20-tetranor-13,14-didehydro-PGF₂, a prostaglandin analog according to claim
 35. 37. A prostaglandin analog according to claim 24, wherein M₁ is ##STR7##
 38. A prostaglandin analog according to claim 37, wherein s is zero or one and T is chloro, fluoro, or trifluoromethyl.
 39. A prostaglandin analog according to claim 38, wherein g is
 3. 40. A prostaglandin analog according to claim 39, wherein at least one of R₃ and R₄ is methyl.
 41. 9-Deoxy-9-methylene-2a,2b-dihomo-16-methyl-16-phenyl-18,19,20-trinor-13,14-didehydro-PGF₂, a prostaglandin analog according to claim
 40. 42. A prostaglandin analog according to claim 39, wherein at least one of R₃ and R₄ is fluoro.
 43. 9-Deoxy-9-methylene-2a,2b-dihomo-16,16-difluoro-16-phenyl-17,18,19,20-tetranor-13,14-didehydro-PGF.sub.2, a prostaglandin analog according to claim
 42. 44. A prostaglandin according to claim 39, wherein R₃ and R₄ are both hydrogen.
 45. 9-Deoxy-9-methylene-2a,2b-dihomo-16-phenyl-17,18,19,20-tetranor-13,14-didehydro-PGF.sub.2, a prostaglandin analog according to claim
 44. 46. A prostaglandin analog according to claim 38, wherein g is one.
 47. A prostaglandin analog according to claim 46, wherein at least one of R₃ and R₄ is methyl.
 48. A prostaglandin analog according to claim 47, wherein R₃ and R₄ are both methyl.
 49. 9-Deoxy-9-methylene-16-methyl-16-phenyl-18,19,20-trinor-13,14-didehydro-PGF₂, tris(hydroxymethyl)aminomethane salt, a prostaglandin analog according to claim
 48. 50. 9-Deoxy-9-methylene-16-methyl-16-phenyl-18,19,20-trinor-13,14-didehydro-PGF₂, methyl ester, a prostaglandin analog according to claim
 48. 51. 9-Deoxy-9-methylene-16-methyl-16-phenyl-18,19,20-trinor-13,14-didehydro-PGF₂, a prostaglandin analog according to claim
 48. 52. A prostaglandin analog according to claim 46, wherein at least one of R₃ and R₄ is fluoro.
 53. A prostaglandin analog according to claim 52, wherein R₃ and R₄ are both fluoro.
 54. A prostaglandin analog according to claim 53, wherein R₅ is methyl.
 55. 9-Deoxy-9-methylene-15-methyl-16,16-difluoro-16-phenyl-17,18,19,20-tetranor-13,14-didehydro-PGF₂, a prostaglandin analog according to claim
 54. 56. A prostaglandin analog according to claim 53, wherein R₅ is hydrogen.
 57. 9-Deoxy-9-methylene-16,16-difluoro-16-phenyl-17,18,19,20-tetranor-13,14-didehydro-PGF₂, a prostaglandin analog according to claim
 56. 58. A prostaglandin analog according to claim 46, wherein R₃ and R₄ are both hydrogen.
 59. A prostaglandin analog according to claim 58, wherein R₅ is methyl.
 60. 9-Deoxy-9-methylene-15-methyl-16-phenyl-17,18,19,20-tetranor-13,14-didehydro-PGF₂, tris(hydroxymethyl)aminomethane salt, a prostaglandin analog according to claim
 59. 61. 9-Deoxy-9-methylene-15-methyl-16-phenyl-17,18,19,20-tetranor-13,14-didehydro-PGF₂, methyl ester, a prostaglandin analog according to claim
 59. 62. 9-Deoxy-9-methylene-15-methyl-16-phenyl-17,18,19,20-tetranor-13,14didehydro-PGF₂, a prostaglandin analog according to claim
 59. 63. A prostaglandin analog according to claim 58, wherein R₅ is hydrogen.
 64. 9-Deoxy-9-methylene-16-phenyl-17,18,19,20-tetranor-13,14didehydro-PGF₂ methyl ester, a prostaglandin analog according to claim
 63. 65. 9-Deoxy-9-methylene-16-phenyl-17,18,19,20-tetranor-13,14-didehydro-PGF₂, a prostaglandin analog according to claim
 63. 